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Mutations in HNF1A result in marked alterations of plasma glycan profile

Research output: Contribution to journalArticle

  • Gaya Thanabalasingham
  • Jennifer E Huffman
  • Jayesh J Kattla
  • Mislav Novokmet
  • Igor Rudan
  • Anna L Gloyn
  • Caroline Hayward
  • Barbara Adamczyk
  • Rebecca M Reynolds
  • Ana Muzinic
  • Neelam Hassanali
  • Maja Pucic
  • Amanda J Bennett
  • Abdelkader Essafi
  • Ozren Polasek
  • Saima A Mughal
  • Irma Redzic
  • Dragan Primorac
  • Lina Zgaga
  • Ivana Kolcic
  • Torben Hansen
  • Daniela Gasperikova
  • Erling Tjora
  • Mark W J Strachan
  • Trine Nielsen
  • Juraj Stanik
  • Iwar Klimes
  • Oluf B Pedersen
  • Pål R Njølstad
  • Sarah H Wild
  • Ulf Gyllensten
  • Olga Gornik
  • James F Wilson
  • Nicholas D Hastie
  • Harry Campbell
  • Mark I McCarthy
  • Pauline M Rudd
  • Katharine R Owen
  • Gordan Lauc
  • Alan F Wright
Original languageEnglish
Pages (from-to)1329-37
Number of pages9
Issue number4
DatePublished - Apr 2013


A recent genome-wide association study identified hepatocyte nuclear factor 1-α (HNF1A) as a key regulator of fucosylation. We hypothesized that loss-of-function HNF1A mutations causal for maturity-onset diabetes of the young (MODY) would display altered fucosylation of N-linked glycans on plasma proteins and that glycan biomarkers could improve the efficiency of a diagnosis of HNF1A-MODY. In a pilot comparison of 33 subjects with HNF1A-MODY and 41 subjects with type 2 diabetes, 15 of 29 glycan measurements differed between the two groups. The DG9-glycan index, which is the ratio of fucosylated to nonfucosylated triantennary glycans, provided optimum discrimination in the pilot study and was examined further among additional subjects with HNF1A-MODY (n = 188), glucokinase (GCK)-MODY (n = 118), hepatocyte nuclear factor 4-α (HNF4A)-MODY (n = 40), type 1 diabetes (n = 98), type 2 diabetes (n = 167), and nondiabetic controls (n = 98). The DG9-glycan index was markedly lower in HNF1A-MODY than in controls or other diabetes subtypes, offered good discrimination between HNF1A-MODY and both type 1 and type 2 diabetes (C statistic ≥ 0.90), and enabled us to detect three previously undetected HNF1A mutations in patients with diabetes. In conclusion, glycan profiles are altered substantially in HNF1A-MODY, and the DG9-glycan index has potential clinical value as a diagnostic biomarker of HNF1A dysfunction.

    Research areas

  • Adolescent, Adult, Biomarkers, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Female, Gene Expression Regulation, Hepatocyte Nuclear Factor 1-alpha, Humans, Male, Middle Aged, Mutation, Missense, Polymorphism, Single Nucleotide, Polysaccharides, Reproducibility of Results, Young Adult, Journal Article, Research Support, Non-U.S. Gov't



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